Aging is characterized by a decline of the potential to adapt to environmental stresses. There is some evidence that aging in individuals is marked by a decline in normal immune cell functions (Makinodan et al., Adv. Immunol. 29:287-330 (1980); Wade et al., Adv. Immunol. 36:143-188 (1984)) and that the decline is due to decrease and changes of the heterogenous lymphoid cell population. (Bocci, V., Biol. Rev, 56:68 (1981). Clinical manifestations include increased incidence of infections, tumors, autoimmune and immune complex diseases. (Bocci, V., Biol. Rev, 56:68 (1981). The immune system deteriorates with aging as shown by decreases in the thymic lymphatic mass (Hirokawa et al., Clin. Immunol. & Immunopathol. 24:251-262 (1982)); the proliferative response of spleen cells to mitogenic or alloantigenic stimulation (Chandra, R. K., Immunol. 67:141-147 (1989); Adler et al., J. Immunol. 107:1357-1362 (1971)) and a decrease in the frequency of occurrence of anti-sheep erythrocyte (SRBC antibody in the spleen after immunization with SRBC (Price et al., J. Immunol. 108:413-417 (1972)). This effect of age is termed immunological senescence. The above noted changes in immunological functions associated with aging, predispose the subject to the onset of various undesired medical conditions, including autoimmune diseases, cancers, and life-threatening infections (Wade et al., Adv. Immunol. 36:143-188 (1984)).
Dietary manipulation (Chandra, R. K., Immunol. 77:141-147 (1989); Kubo et al., J. Nutr. 114:1884-1899 (1984); Gabrielsen et al., Nature 264:439-440 (1976)) and cell grafting (Hirokawa et al., Clin. Immunol. & Immunopathol. 24:251-262 (1982); Price et al., J. Immunol. 108:413-417 (1972)) have been proposed as treatments for the prevention or restoration of the above age-related changes in immunological functions. The disclosed methods for prevention of senescence in the immune system could help to decrease the life threatening risks associated with aging. However, dietary manipulation only slightly decreases life threatening risks associated with aging, while cell grafting is an experimental procedure requiring the use of immunosuppressive drugs to eliminate rejection of the graft. (Chandra, R. K., Immunol. 67:141-147 (1989)).
Wade et al. discusses the interaction between gut-associated lymphoid tissues (GALT) and the prevention of invasion of enteric bacteria (Wade et al., Adv. Immunol. 36:143-188 (1984)). GALT are composed of non-organized lymphoid components including intraepithelial lymphocytes (IEL) and lamina propia lymphocytes, and organized lymphoid components such as mesenteric lymph nodes (MLN) and Peyer's patches. The involvement of these cells in the defense against translocation of intestinal microflora in aged individuals, and/or immunological senescence in aged individuals is not clear. Rodney D. Berg reported that translocation of indigenous enteric bacteria from the GI tract does not occur in healthy, adult animals, but does occur in animals when (i) the permeability of the intestinal epithelium is altered, (ii) when there is abnormally high population levels of intestinal bacteria, and (iii) when the animal's immune system is compromised (Berg, Rodney D., "Human & Intestinal Microflora in Health and Disease," Chap. 15:38-346 (1983)).
Currently, there are two known but problematic ways of protecting against the invasion of enteric bacteria. The first involves eliminating or reducing the number of intestinal pathogenic bacteria. Mastromarino et al. report that antibiotic administration significantly protects from the invasion of bacteria (Mastromarino et al., Radiat. Res. 68:329-338 (1976)). However, antibiotic administration also increases the susceptibility of a host to colonization by antibiotic resistant pathogens. This colonization in turn causes senile indigenous infectious disease. Further, Berg reports that the "indiscriminate use of oral antibiotics may disrupt the intestinal bacterial ecology, promoting bacterial translocation and placing patients at even greater risk for opportunistic infections" (Berg, Rodney D., "Human Intestinal Microflora in Health and Disease," Chap. 15:342 (1983)). A second way to protect an individual from the invasion of enteric bacteria, that is, to protect from indigenous infection, is to specifically or nonspecifically augment the host's defense mechanisms against bacterial infection. Potent macrophage activators such as Corynebacterium parvum have been reported to decrease the rate of translocation of intestinal Escherichia coli in mice (Yoshikai et al., Microbiol. Immunol. 27:273-282 (1983)). Bovine milk immunoglobulin has also been reported to be effective in the prevention of enterotoxin E. coli or rotavius infections (Tacket et al., N. Engl. J. Med. 318:1240-1243 (1988); Hilpert et al., J. Infect. Dis. 156:158-166 (1987)).